Abstract
Purpose :
Substance P (SP) is a well-known modulator of pain and has been shown to modulate nociception in the murine cornea. The purpose of this study was to determine whether the inhibition of SP can reduce ocular pain following corneal chemical injury by local antagonism of SP’s preferred receptor, neurokinin 1 receptor (NK1R).
Methods :
Corneal alkali burn was induced in C57BL/6 mice by placing a paper disc (2-mm diameter) soaked in 1 N NaOH for 10 seconds on the central cornea. 6 mice with 1:1 sex ratio were used for each experiment. SP protein levels in the cornea and trigeminal ganglion (TG) were measured by ELISA at 4, 7, 14, 21, and 28 days after alkali burn induction. Animals were randomized into two groups receiving L-733,060 (1μg/μl) or PBS, topically twice a day for 4 weeks after alkali burn. On day 4, 7, 14, 21 and 28, eye wiping test (EWT) was performed to evaluate hyperalgesia after applying hypertonic saline (2M NaCl) as noxious stimulus. Following EWT, allodynia was assessed by quantifying palpebral ratio (PR) via an automated video analysis of the animals’ eye after instillation of a saline solution iso-osmolar to tears (0.9 % NaCl) as innocuous stimulus.
Results :
The SP levels in the corneas at 4, 7, 14, 21, and 28 days after alkali burn were 9465 ± 1625, 12721 ± 2088, 12536 ± 831, 12476 ± 3402, and 11145 ± 647 pg/mg, respectively. Compared with the SP level of naive corneas (8155 ± 483 pg/mg), there were significant increases in the SP levels of the corneas on days 7, 14, 21, and 28 after alkali burn (P<0.001, P< 0.001, P<0.001, P<0.01, respectively). Meanwhile, the SP levels in TG had no significant change at any time point after alkali burn. Eye wipe behavior was significantly higher in PBS group compared to normal mice at all time points after alkali burn. L-733,060 group showed significant decreases in the behavior compared to PBS group at day 4, 14, 21, 28 (P < 0.01, P < 0.01, P < 0.01, P < 0.05, respectively). Similarly, PR was significantly lower in PBS group compared to normal mice at all time points after alkali burn. L-733,060 group showed significant increases in PR at day 4, 14, 21, 28 (P < 0.01, P < 0.05, P < 0.01, P < 0.05, respectively).
Conclusions :
Our data demonstrate that NK1R antagonist reduces ocular pain in the murine alkali burn model.
This abstract was presented at the 2023 ARVO Annual Meeting, held in New Orleans, LA, April 23-27, 2023.